Journal Article

Proton pump inhibitors and risk of gastric cancer: population-based cohort study

Barkun, Alan N, Azoulay, Laurent, Abrahami, Devin, Schnitzer, Mireille E, Suissa, Samy, McDonald, Emily Gibson

2022

Overview

ObjectiveTo determine whether new users of proton pump inhibitors (PPIs) are at an increased risk of gastric cancer compared with new users of histamine-2 receptor antagonists (H2RAs).DesignUsing the UK Clinical Practice Research Datalink, we conducted a population-based cohort study using a new-user active comparator design. From 1 January 1990 to 30 April 2018, we identified 973 281 new users of PPIs and 193 306 new users of H2RAs. Cox proportional hazards models were fit to estimate HRs and 95% CIs of gastric cancer, and the number needed to harm was estimated using the Kaplan-Meier method. The models were weighted using standardised mortality ratio weights using calendar time-specific propensity scores. Secondary analyses assessed duration and dose–response associations.ResultsAfter a median follow-up of 5.0 years, the use of PPIs was associated with a 45% increased risk of gastric cancer compared with the use of H2RAs (HR 1.45, 95% CI 1.06 to 1.98). The number needed to harm was 2121 and 1191 for five and 10 years after treatment initiation, respectively. The HRs increased with cumulative duration, cumulative omeprazole equivalents and time since treatment initiation. The results were consistent across several sensitivity analyses.ConclusionThe findings of this large population-based cohort study indicate that the use of PPIs is associated with an increased risk of gastric cancer compared with the use of H2RAs, although the absolute risk remains low.

• Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology,BMJ Publishing Group LTD
• Subject: acid-related diseases / Acids / Bias / Calendars / Cancer therapies / Clinical medicine / Cohort analysis / Cohort Studies / Drug dosages / epidemiology / Female / Gastric cancer / Histamine / Histamine H2 Antagonists - adverse effects / Histamine H2 receptors / Humans / Male / Middle Aged / Omeprazole / Population / Population studies / Population-based studies / Prescription drugs / Proportional Hazards Models / Proton pump inhibitors / Proton Pump Inhibitors - adverse effects / Sensitivity analysis / Skin cancer / Stomach / Stomach Neoplasms - chemically induced / Stomach Neoplasms - epidemiology / United Kingdom - epidemiology / Variables